Most patients with advanced B-lineage malignancies who are beyond first relapse and subsequently attain a state of remission, or at least a state of minimal-residual disease, are eligible for allogeneic hematopoietic stem-cell transplantation (HSCT). The introduction of umbilical cord blood (UCB) as an alternative source of allogeneic hematopoietic stem cells (HSC) for patients without a suitable human leukocyte antigen (HLA)-matched donor is a major advance for the field of allogeneic HSCT. Major advantages of umbilical cord blood transplantation (UCBT) include (i) rapid procurement of the allograft, (ii) increased likelihood of finding a match for a minority patient, (iii) requirement for less-stringent HLA matching, and (iv) decreased incidence of graft-versus-host disease (GVHD). However, relapse remains a major barrier to the therapeutic potential of UCBT. The adoptive transfer of T cells expressing a second generation CD19-specific chimeric antigen receptor (CAR) has been shown to cure some patients with advanced B-cell malignancies. This proposal seeks to apply this adoptive immunotherapy to prevent relapse after allogeneic umbilical cord blood transplantation in the setting of a first-in-human clinical Phase 1 protocol that targets B-cell malignancies. The clinica impact is based upon targeting CD19, a B-lineage antigen expressed on malignant B cells. The Sleeping Beauty (SB) DNA plasmid transposon/transposase system will be used, which (i) avoids current problems other investigators are currently experiencing manufacturing clinical-grade lentivirus for gene transfer of the chimeric antigen receptor (CAR) transgene, and (ii) by using a non-viral system reduces cost compared to transducing T cells with clinical-grade recombinant retro- and lentivirus. Umbilical cord blood-derived CAR positive T cells can be rapidly and selectively propagated to clinically-sufficient numbers on designer artificial antigen presenting cells (aAPC) expressing CD19. This avoids the time and expense needed to manufacture clinical-grade recombinant retrovirus to transduce T cells. This can be achieved from small amounts of UCB to avoid compromising hematopoiesis in the recipient. This proposal seeks to: Aim #1, infuse graded doses of CD19-specific, genetically modified, T cells and evaluate combination immunotherapy in patients with advanced B-lineage malignancies after allogeneic UCBT; Aim #2, undertake the primary objectives to establish safety, feasibility, and persistence of a single dose of UCB-derived genetically modified T cells. An intra-patient dosing scheme will determine whether the amount of T cells infused alters persistence of chimeric antigen receptor positive T cells which is predicted to impact their therapeutic potential Aim #3, undertake secondary objectives to determine immune response(s) to the transgenes; trafficking of CAR+ T cells; development of oligoclonal sub-population(s) of infused T cells; emergence of genetically modified T cells with effector memory, central memory, stem-cell-like, and/or naive immunophenotypes; and maintenance of CD19- redirected effector functions.